Hypercholesterolaemia
Conditions
Keywords
Hypertension, hypercholesterolemia, siRNA, inclisiran, QCZ484, randomized, double-blind, Phase 2, pharmacodynamics, AGT, PCSK9
Brief summary
This is a multicenter, randomized, double-blind, factorial design Phase 2 study to evaluate the pharmacodynamics, safety and tolerability of a combination of QCZ484 and inclisiran compared to QCZ484, inclisiran, and placebo in participants with hypertension and concomitant hypercholesterolemia.
Detailed description
The study will last up to 12 months and has three periods: * Eligibility will be assessed during the screening period including 2 screening visits. Some eligibility criteria will be confirmed at the Baseline/Randomization visit. * Eligible participants will be randomized to receive a combination of QCZ484 and inclisiran, QCZ484, inclisiran or placebo once on Day 1 at the Baseline/Randomization visit. * Afterwards, participants will enter the safety follow-up period. Eligible participants who complete the treatment period have the option to participate in an open-label extension study instead of entering the safety follow-up period.
Interventions
DRUGQCZ484
QCZ484 once on Day 1
DRUGInclisiran
Inclisiran once on Day 1
DRUGQCZ484 placebo
QCZ484 placebo once on Day 1
DRUGInclisiran placebo
Inclisiran placebo once on Day 1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males or females aged 18 to 75 years. * Diagnosis of primary hypertension. * Treatment with either no, or up to 2 antihypertensive medications at a stable dose for at least 4 weeks preceding screening. * Systolic blood pressure ≥140 and \<165 mmHg based on the mean of 3 sitting measurements based on office blood pressure monitoring. * Diagnosis of hypercholesterolemia including heterozygous familial hypercholesterolemia unable to reach LDL-C goals with a stable dose of statin treatment for at least 4 weeks prior to screening as per Investigator judgement, guidelines and local practice (if tolerated and not contraindicated) with or without bempedoic acid and with or without ezetimibe prescribed according to local guidance, at a stable dose for at least 4 weeks preceding Screening Visit 1. The following parameters must be confirmed at Screening Visit 2: * Fasting serum LDL-C ≥70 mg/dL and \<190 mg/dL using Friedewald equation. * Fasting triglyceride \<400 mg/dL.
Exclusion criteria
* Symptomatic orthostatic hypotension. * Treatment with certain medications and/or unable to comply with prohibited medications requirements. Other protocol inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline of PCSK9 levels | Baseline and Month 3 | Percent (%) change from baseline of PCSK9 levels for QCZ484 + Inclisiran at Month 3 |
| Percent change from baseline of AGT levels | Baseline and Month 3 | Percent (%) change from baseline of AGT levels for QCZ484 + Inclisiran at Month 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of systolic blood pressure | Baseline, Month 3 and Month 6 | Change from baseline of systolic blood pressure for QCZ484 + Inclisiran at Month 3 and 6. |
| Change from baseline of LDL-C levels | Baseline, Month 3 and Month 6 | Change from baseline of LDL-C levels for QCZ484 + Inclisiran at Month 3 and 6. |
| Number of participants with Treatment-emergent adverse event and abnormal changes in laboratory parameters, vital signs and other safety assessments | Up to month 12 | Number of participants with treatment-emergent adverse event, abnormal changes in laboratory parameters, vital signs and other safety assessments up to Month 12. |
Countries
United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed